Current understandings and perspectives on non-cancer health effects of benzene: A global concern

Objective

Benzene, as a volatile organic compound, is known as one of the main air pollutants in the environment. The aim of this review is to summarize all available evidences on non-cancerous health effects of benzene providing an overview of possible association of exposure to benzene with human chronic diseases, specially, in those regions of the world where benzene concentration is being poorly monitored.

Methodology

A bibliographic search of scientific databases including PubMed, Google Scholar, and Scirus was conducted with key words of “benzene toxic health effects”, “environmental volatile organic compounds”, “diabetes mellitus and environmental pollutants”, “breast cancer and environmental pollution”, “prevalence of lung cancer”, and “diabetes prevalence”. More than 300 peer reviewed papers were examined. Experimental and epidemiologic studies reporting health effects of benzene and volatile organic compounds were included in the study.

Results

Epidemiologic and experimental studies suggest that benzene exposure can lead to numerous non-cancerous health effects associated with functional aberration of vital systems in the body like reproductive, immune, nervous, endocrine, cardiovascular, and respiratory.

Conclusion

Chronic diseases have become a health burden of global dimension with special emphasis in regions with poor monitoring over contents of benzene in petrochemicals. Benzene is a well known carcinogen of blood and its components, but the concern of benzene exposure is more than carcinogenicity of blood components and should be evaluated in both epidemiologic and experimental studies. Aspect of interactions and mechanism of toxicity in relation to human general health problems especially endocrine disturbances with particular reference to diabetes, breast and lung cancers should be followed up.     

Short-term effects of electronic and tobacco cigarettes on exhaled nitric oxide

The objective of this study was to compare the short-term respiratory effects due to the inhalation of electronic and conventional tobacco cigarette-generated mainstream aerosols through the measurement of the exhaled nitric oxide (eNO). To this purpose, twenty-five smokers were asked to smoke a conventional cigarette and to vape an electronic cigarette (with and without nicotine), and an electronic cigarette without liquid (control session).     

What Does a Mathematical Model Tell About the Impact of Reinfection in Korean Tuberculosis Infection?

Objectives

According to the Korea Centers for Disease Control and Prevention, new active tuberculosis (TB) cases have increased since 2001. Some key factors explain and characterize the transmission dynamics of Korean TB infection, such as a higher ratio of latent individuals and a new reporting system implemented in 2001, among others.

Methods

We propose a mathematical TB model that includes exogenous reinfection to gain a better understanding of the recent trend for TB incidence. We divide the simulation time window into two periods, 1970–2000 and 2001–2012, according to the implementation date of a new TB detection system.

Results

Two sets of parameters, including the transmission rate, the latent period, the recovery rate, and the proportion of exogenous reinfection, are estimated using the least-squares method and calibrated to data on the incidence of active TB.

Conclusion

Among some key parameters in the model, the case finding effort turned out to be the most significant impacting component on the reduction in the active TB cases.     

Cannabidiol inhibits paclitaxel-induced neuropathic pain through 5-HT1A receptors without diminishing nervous system function or chemotherapy efficacy

Background and Purpose

Paclitaxel (PAC) is associated with chemotherapy-induced neuropathic pain (CIPN) that can lead to the cessation of treatment in cancer patients even in the absence of alternate therapies. We previously reported that chronic administration of the non-psychoactive cannabinoid cannabidiol (CBD) prevents PAC-induced mechanical and thermal sensitivity in mice. Hence, we sought to determine receptor mechanisms by which CBD inhibits CIPN and whether CBD negatively effects nervous system function or chemotherapy efficacy.

Experimental Approach

The ability of acute CBD pretreatment to prevent PAC-induced mechanical sensitivity was assessed, as was the effect of CBD on place conditioning and on an operant-conditioned learning and memory task. The potential interaction of CBD and PAC on breast cancer cell viability was determined using the MTT assay.

Key Results

PAC-induced mechanical sensitivity was prevented by administration of CBD (2.5 – 10 mg·kg⁻¹) in female C57Bl/6 mice. This effect was reversed by co-administration of the 5-HT_1A antagonist WAY 100635, but not the CB₁ antagonist SR141716 or the CB₂ antagonist SR144528. CBD produced no conditioned rewarding effects and did not affect conditioned learning and memory. Also, CBD + PAC combinations produce additive to synergistic inhibition of breast cancer cell viability.

Conclusions and Implications

Our data suggest that CBD is protective against PAC-induced neurotoxicity mediated in part by the 5-HT_1A receptor system. Furthermore, CBD treatment was devoid of conditioned rewarding effects or cognitive impairment and did not attenuate PAC-induced inhibition of breast cancer cell viability. Hence, adjunct treatment with CBD during PAC chemotherapy may be safe and effective in the prevention or attenuation of CIPN.     

Long-Acting Atypical Antipsychotics: Characterization of the Local Tissue Response

Purpose

Long-acting injectables (LAIs) are increasingly recognized as an effective therapeutic approach for treating chronic conditions. Many LAIs are formulated to create a poorly soluble depot from which the active agent is delivered over time. This long residing depot can cause localized chronic-active inflammation in the tissue, which has not been well defined in the literature. The purpose of this work is to establish an experimental baseline for describing these responses.

Methods

Non-human primates and rodents were used to examine the response to LAI formulations of two clinically relevant atypical antipsychotics, aripiprazole monohydrate and olanzapine pamoate monohydrate.

Results

A foreign body response develops with elevations of key cytokines such as IL-1α, IL-1β, TNFα, and IL6 at the site of injection. However, the tissue response for the two atypical antipsychotics compounds diverge as evidenced by quantitative differences observed in cytokine levels at various time points after dosing.

Conclusions

Our studies show that, while the drugs are in the same therapeutic class, the response to each of these compounds can be distinguished qualitatively and quantitatively, supporting the idea that the injection site reaction involves a multiplicity of factors including the properties of the compound and cellular dynamics at the site of injection.     

Amphetamine Self-Administration Attenuates Dopamine D2 Autoreceptor Function

Dopamine D2 autoreceptors located on the midbrain dopaminergic neurons modulate dopamine (DA) neuron firing, DA release, and DA synthesis through a negative-feedback mechanism. Dysfunctional D2 autoreceptors following repeated drug exposure could lead to aberrant DA activity in the ventral tegmental area (VTA) and projection areas such as nucleus accumbens (NAcc), promoting drug-seeking and -taking behavior. Therefore, it is important to understand molecular mechanisms underlying drug-induced changes in D2 autoreceptors. Here, we reported that 5 days of amphetamine (AMPH) self-administration reduced the ability of D2 autoreceptors to inhibit DA release in the NAcc as determined by voltammetry. Using the antibody-capture [³⁵S]GTPγS scintillation proximity assay, we demonstrated for the first time that midbrain D2/D3 receptors were preferentially coupled to Gαi2, whereas striatal D2/D3 receptors were coupled equally to Gαi2 and Gαo for signaling. Importantly, AMPH abolished the interaction between Gαi2 and D2/D3 receptors in the midbrain while leaving striatal D2/D3 receptors unchanged. The disruption of the coupling between D2/D3 receptors and Gαi2 by AMPH is at least partially explained by the enhanced RGS2 (regulator of G-protein signaling 2) activity resulting from an increased RGS2 trafficking to the membrane. AMPH had no effects on the midbrain expression and trafficking of other RGS proteins such as RGS4 and RGS8. Our data suggest that midbrain D2/D3 receptors are more susceptible to AMPH-induced alterations. Reduced D2 autoreceptor function could lead to enhanced DA signaling and ultimately addiction-related behavior. RGS2 may be a potential non-dopaminergic target for pharmacological intervention of dysfunctional DA transmission and drug addiction.     

Images of alcohol among Italian adolescents. Understanding their point of view

Aims: This study aims to plug the gap about how young people understand their direct and indirect experience with alcohol by investigating the prevalent images of alcohol among 15-year-olds. The study also aims to clarify the position of young Italians towards traditional Italian drinking culture.

Methods: Twenty-two focus groups were organized in two Italian towns, Torino and Cosenza. The focus groups (FGs) used the Reception Analytical Group Interview (RAGI) method, wherein respondents are invited to discuss after seeing video clips used as a stimulus. The material thus collected was analysed through an approach that takes both the participants’ interpretative processes and their socio-cultural environment into consideration.

Findings: Using ‘drinking situations’ as an analytical tool, it was found that young people's images about drinking are still in line with tradition, as are the importance assigned to social drinking and the stigma attached to intoxication. Young people also appear to be aware of the negative consequences of drinking, even if the risks related to pharmaceutical use seem to be underestimated.

Conclusions: Results cast doubt on the supposed convergence of drinking patterns within Europe and provide useful insights for the development of alcohol use and abuse policies and prevention.     

High Magnesium and Sirolimus on Rabbit Vascular Cells—An In Vitro Proof of Concept

Drug-eluting bioresorbable scaffolds represent the last frontier in the field of angioplasty and stenting to treat coronary artery disease, one of the leading causes of morbidity and mortality worldwide. In particular, sirolimus-eluting magnesium-based scaffolds were recently introduced in clinical practice. Magnesium alloys are biocompatible and dissolve in body fluids, thus determining high concentrations of magnesium in the local microenvironment. Since magnesium regulates cell growth, we asked whether high levels of magnesium might interfere with the antiproliferative action of sirolimus. We performed in vitro experiments on rabbit coronary artery endothelial and smooth muscle cells (rCAEC and rSMC, respectively). The cells were treated with sirolimus in the presence of different concentrations of extracellular magnesium. Sirolimus inhibits rCAEC proliferation only in physiological concentrations of magnesium, while high concentrations prevent this effect. On the contrary, high extracellular magnesium does not rescue rSMC growth arrest by sirolimus and accentuates the inhibitory effect of the drug on cell migration. Importantly, sirolimus and magnesium do not impair rSMC response to nitric oxide. If translated into a clinical setting, these results suggest that, in the presence of sirolimus, local increases of magnesium concentration maintain normal endothelial proliferative capacity and function without affecting rSMC growth inhibition and response to vasodilators.     

Customized Root-Analogue Implants: A Review on Outcomes from Clinical Trials and Case Reports

(1) It is estimated that 10% of the world’s population will need a dental implant in their lifetime. Despite all the advances in the comprehension of dental implant designs, materials and techniques, traditional implants still have many limitations. Customized root-analogue implants are, therefore, gaining increased interest in dental rehabilitation and are expected to not only preserve more hard and soft tissues but also avoid a second surgery and improve patient overall satisfaction. In this sense, the aim of this review was to collect and analyse the clinical trials and case reports on customized root-analogue implants available in the literature; (2) This review was carried out according to the PRISMA Statement. An electronic database search was performed using five databases: PubMed, Google Scholar, Medline, Science Direct, and Scopus. The following keywords were used for gathering data: custom-made, dental implants, root-analogue, anatomical, customized and tooth-like; (3) 15 articles meeting the inclusion criteria—articles reporting clinical trials, case reports or animal studies and articles with root-analogue implants and articles with totally customized implant geometries—were selected for the qualitative synthesis. The design and manufacturing techniques, implant material and surface treatments were assessed and discussed; (4) The performance of some root-analogue implants with specific features (i.e., macro-retentions) was successful, with no signs of infection, periodontitis nor bleeding during the follow-up periods.     

Foam Replica Method in the Manufacturing of Bioactive Glass Scaffolds: Out-of-Date Technology or Still Underexploited Potential?

Since 2006, the foam replica method has been commonly recognized as a valuable technology for the production of highly porous bioactive glass scaffolds showing three-dimensional, open-cell structures closely mimicking that of natural trabecular bone. Despite this, there are important drawbacks making the usage of foam-replicated glass scaffolds a difficult achievement in clinical practice; among these, certainly the high operator-dependency of the overall manufacturing process is one of the most crucial, limiting the scalability to industrial production and, thus, the spread of foam-replicated synthetic bone substitutes for effective use in routine management of bone defect. The present review opens a window on the versatile world of the foam replica technique, focusing the dissertation on scaffold properties analyzed in relation to various processing parameters, in order to better understand which are the real issues behind the bottleneck that still puts this technology on the Olympus of the most used techniques in laboratory practice, without moving, unfortunately, to a more concrete application. Specifically, scaffold morphology, mechanical and mass transport properties will be reviewed in detail, considering the various templates proposed till now by several research groups all over the world. In the end, a comprehensive overview of in vivo studies on bioactive glass foams will be provided, in order to put an emphasis on scaffold performances in a complex three-dimensional environment.